Human T-cell lymphotrophic viruses are composed of at least three members including the HTLV-I virus which is the etiologic agent of adult T-cell leukemia/lymphoma and the recently well characterized HTLV-III (ARV, LAV) genome which transmits acquired immune deficiency syndrome (AIDS). The objective of this proposal is to make use of the lymphotrophic nature of the HTLV-I virus in the construction of a defective packaging line which would allow for encapsidation and transmission of defective HTLV-I viral genomes. Various subgenomic regions of HTLV-I will be subcloned into an HTLV-I based vector in the anti-sense orientations to access the effects of these anti-sense transcripts on virus production. Analysis of an experimental model of this sort which displays both cellular and intracellular target specificity for regulating viral expression, could have therapeutic implications for the eventual control of HTLV-I induced ATLL.